Evaluating Dupilumab for Netherton Syndrome

A Randomized Double-blinded Pilot Study of the Efficacy and Safety of Dupilumab Versus Placebo in Patients With Netherton Syndrome

This study is testing if a medication called dupilumab can improve skin condition and quality of life for people with moderate to severe Netherton Syndrome compared to a placebo.

Quick facts

• Phase: Phase2; Phase3
• Study type: Interventional
• Enrollment: 24 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: University Hospital, Toulouse (Academic / other)
• Drugs / interventions: dupilumab, methotrexate
• Locations: 2 sites (Paris and 1 other locations)
• Trial ID: NCT04244006 on ClinicalTrials.gov

What this trial studies

This pilot study aims to assess the efficacy and safety of dupilumab compared to a placebo in patients with moderate to severe Netherton Syndrome (NS). Participants will be randomly assigned to receive either dupilumab or placebo over a 16-week period, with doses administered every two weeks. The study focuses on measuring improvements in skin condition and quality of life, addressing the significant unmet medical need for effective therapies in NS. The trial is designed to provide insights into the potential benefits of dupilumab for managing this chronic skin condition.

Who should consider this trial

Good fit: Ideal candidates are adults diagnosed with moderate to severe Netherton Syndrome who meet specific clinical criteria.

Not a fit: Patients with hypersensitivity to dupilumab or those currently using certain immunosuppressive treatments may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could significantly improve skin condition and quality of life for patients with Netherton Syndrome.

How similar studies have performed: While there have been limited case reports on therapies targeting skin inflammation in Netherton Syndrome, this approach with dupilumab is novel and has not been extensively tested.

Eligibility criteria

Inclusion Criteria:

* Adult patients affiliated to a social insurance protection regimen.
* Clinical diagnosis of NS (7) (trichorrhexis invaginata, extensive scaling, skin inflammation, allergic manifestations) and absent or marked reduction of LEKTI staining.
* Moderate to severe forms: NASA (Netherton Area Severity Assessment score) score ≥ 5/12 at inclusion.
* Patients able to understand the study procedures including the ability to complete patient-based self-assessment questionnaires.
* Patients who agree to sign the written informed consent.

Exclusion Criteria:

* Hypersensitivity to dupilumab or its excipients.
* Modification of the usual treatment (emollients and topical corticosteroids used on a regular basis) within 2 weeks before inclusion.
* Treatment with topical calcineurin inhibitors 1 week before inclusion.
* Treatment with oral immunosuppressant (including cyclosporine, methotrexate, azathioprine, mycophenolate mofetil), oral retinoids (acitretin, alitretinoin, isotretinoin) or phototherapy within 4 weeks before inclusion.
* Treatment with immunomodulating biologics (Tumor Necrosis Factor (TNF) inhibitor) 16 weeks before inclusion.
* Treatment with another investigational drug within 8 weeks before inclusion.
* Treatment with a systemic antibiotic within 2 weeks before inclusion.
* Active skin infection requiring the use of a systemic therapy within 2 weeks before the inclusion.
* Any other condition that according to the investigator will impair the ability to evaluate treatment effect.
* Known or suspected history of immunosuppression, including history of invasive opportunistic infections (e.g., tuberculosis, histoplasmosis, listeriosis, coccidioidomycosis, pneumocystis, aspergillosis).
* Current infections including infection with helminthes.
* Pregnant or breastfeeding women, or women planning to become pregnant or breastfeed during the study. Women of childbearing age, potentially sexually active, and unwilling to use adequate birth control methods.
* Mental or physical incapacity to fill in the questionnaires.

Where this trial is running

Paris and 1 other locations

• Dermatologie Necker — Paris, France (Not_yet_recruiting)
• Dermatology — Toulouse, France (Recruiting)

Study contacts

• Principal investigator: Juliette MAZEREEUW-HAUTIER — Toulouse Hospital
• Study coordinator: Nadège ALGANS

Conditions Netherton Syndrome